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Biomedical subjects

Jacques Reynes

Publications and source records attributed to Jacques Reynes.

At least 19 recordsLinked to original sources
PubMed2006

Fat microinfiltration autografting for facial restructuring in HIV patients.

INTRODUCTION: Antiretroviral drugs used to treat HIV infection are closely associated with faciocervical and peripheral lipodystrophies. There are several options for surgical treatment of facial lipodystrophy, one of these was described by S. R. Coleman in 1994, the technique of fat transplantation. MATERIAL AND METHODS: A retrospective study of 23 seropositive patients is presented, who were treated according to Coleman's technique. The surgical procedure was evaluated by clinical and CT analysis. The longest follow-up was 3 years. RESULTS: The technique was well tolerated from both a clinical and psychological point of view. 74% were successful. Multiple fat transplantation procedures were required to obtain a satisfactory result for the remaining patients. No complications were observed. DISCUSSION: Coleman's method is very simple. It is performed without using any biomaterial. There are aesthetic and social benefits for the patients. A limitation of this procedure is that some patients do not have enough fat at the donor site. CONCLUSION: The results of this procedure after a maximum of 3 years postoperatively have been positive. However, there is a need of long-term experience with this method.

Adipose Tissue↗
PubMed2006

Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma.

PURPOSE: To evaluate the safety and efficacy of rituximab adjunction to the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma. PATIENTS AND METHODS: HIV-seropositive patients with high-grade lymphoma of B-cell origin were eligible if they had no more than one of the following characteristics: CD4 cell count less than 100/microL, prior AIDS, or performance status less than 2. This multicenter phase II trial evaluated the response rate and disease-free survival after six courses of rituximab plus CHOP. Results Sixty-one patients were enrolled. All the patients were assessable for safety and 52 were assessable for the tumor response after treatment completion. Characteristics of patients were median age, 41 years; median CD4 cells, 172/microL; histology, diffuse large B-cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16), and plasmablastic (n = 1); 42 patients with stage III to IV; International Prognostic Index 0 to 1 (n=31), and 2 to 3 (n = 27). Grade 3 or 4 toxicity consisted of febrile neutropenia in nine patients, anemia in 16 patients, and thrombocytopenia in five patients. Complete remission (CR) or unconfirmed CR was achieved in 40 of the 52 assessable patients, partial remission was achieved in five patients, and seven patients experienced progression. Forty-three patients were alive after a median follow-up of 33 months. The estimated 2-year overall survival rate was 75% (95% CI, 64% to 86%). Eighteen patients died: 16 as a result of lymphoma, one as a result of infection, and one as a result of encephalitis. CONCLUSION: Rituximab adjunction to CHOP produced a CR rate of 77% and a 2-year survival rate of 75% in patients with AIDS-related non-Hodgkin's lymphoma, without increasing the risk of life-threatening infections.

Adult↗
PubMed2006

The efficiency of R5 HIV-1 infection is determined by CD4 T-cell surface CCR5 density through G alpha i-protein signalling.

OBJECTIVE AND DESIGN: The intensity of replication of CCR5-using HIV-1 strains is highly dependent on the number of CCR5 molecules on the surface of CD4-positive T cells. The molecular mechanisms responsible for this phenomenon remained so far unclear. As CCR5 co-receptors are coupled to G alpha i and G alpha q proteins, we tested the hypothesis that the activation triggered through these proteins secondary to the interaction between the viral envelope and CCR5 could account for the effect of the level of CCR5 expression on HIV-1 production. METHODS: We transduced the wild-type or a G-protein signalling-defective CCR5 gene into CD4/CCR5 HOS cells and peripheral blood mononuclear cells. The effect on cell activation in presence of a CCR5-binding chemokine and on HIV infection was monitored by measuring calcium mobilization and p24 antigen production, respectively. The role of G alpha i protein signalling was tested by adding pertussis toxin to the cell cultures or by transfecting small interfering (si) RNAs into the HOS cells. RESULTS: The over-expression of the wild-type form, but not of a G-protein signalling-defective form of CCR5, on the surface of CCR5 expressing peripheral blood mononuclear cells markedly increased their infectability. In addition, both pertussis toxin and G alpha i 1-specific siRNA drastically inhibited R5 infection. CONCLUSIONS: The signalling through G alpha i-protein induced upon R5 virion binding to CCR5 is responsible for the difference in HIV-1 infectability between CD4-positive T cells expressing low or high levels of cell surface CCR5 density. This observation sheds new light on the physiopathology of HIV infection, and opens new therapeutic opportunities targeting G alpha i signalling.

CD4-Positive T-Lymphocytes↗
PubMed2006

Molecular diagnosis of culture-negative cerebral nocardiosis due to Nocardia abscessus.

We describe a case of culture-negative cerebral nocardiosis in a 34-year-old immunocompetent man who presented multiple cerebral abscesses. All bacteriologic cultures were negative. Nocardiosis was diagnosed by using a direct genus-specific 16S rDNA amplification method, and Nocardia abscessus was identified by hsp65 sequence analysis. The patient is alive and well on imipenem and doxycycline therapy, 14 months after onset.

Adult↗
PubMed2006

Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a protease-inhibitor-containing antiretroviral therapy.

OBJECTIVE: To examine the relationship between plasma levels of apolipoproteins C3 (APOC3) and E (APOE) and the presence of lipid and carbohydrate metabolism abnormalities or clinical signs of lipodystrophy in HIV-1-infected patients started with a protease-inhibitor-containing antiretroviral therapy. METHODS: The Aproco (Antiproteases Cohort) Study enrolled 1,181 HIV-1-infected adults in 47 French healthcare centres from May 1997 to June 1998. From December 1998 through July 1999, the APROCO-Metabolic Complications (APROCO-MC) cross-sectional study was performed at the month 20 visit for those patients enrolled in 1997 and at the month 12 visit for those enrolled in 1998. The current analysis presents results from a subset of patients who had undergone additional tests to measure APOC3 and APOE in order to study their relationship with metabolic syndrome (n=157) and abnormal results in an oral glucose tolerance test (n=135). RESULTS: Increases in triglycerides and non-high-density lipoprotein (HDL) cholesterol were associated with significantly higher levels of APOC3, in both Lp B (lipoproteins containing apolipoprotein B) and Lp non-B (lipoproteins free of apolipoprotein B), and a significant higher level of APOE Lp B. APOC3 and APOC3 Lp non-B were increased when glucose metabolism abnormalities were more severe. The presence of a metabolic syndrome was associated with increased plasma APOC3, APOC3 Lp B and APOC3 Lp non-B levels. In a multiple regression analysis, high levels of APOC3 in Lp B and APOC3 Lp non-B were associated with the presence of clinical signs of lipodystrophy, even after adjustment for triglycerides and HDL-cholesterol levels. CONCLUSIONS: Lipid and/or glucose metabolism abnormalities in treated HIV-1-infected patients are associated with increased levels of APOC3 and, to a lesser extent, APOE plasma concentrations. Increased values are also related to clinical signs of insulin resistance and lipodystrophy.

Adult↗
PubMed2005

Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks.

BACKGROUND: Antiretroviral tolerability is a critical factor contributing to treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO) studies assessed the safety and efficacy of enfuvirtide in treatment-experienced HIV-1-infected patients. METHODS: A total of 997 patients were randomized at a 2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n = 663) or an optimized background regimen alone (control group; n = 334). Control patients could switch to enfuvirtide on virologic failure. RESULTS: In total, 26.5% of patients randomized to enfuvirtide and 36.6% to the control group discontinued study treatment before week 48; the percentage of patients withdrawn for safety reasons (including adverse events [AEs], deaths, and laboratory abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group. Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led to treatment discontinuation in 4.4%. Treatment-related (defined as possibly, probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most frequently reported AEs, were significantly less frequent with enfuvirtide than in the control group. Pneumonia was significantly more frequent in patients treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the incidence was within expected ranges for this population. Lymphadenopathy was also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient-years) for control patients. CONCLUSION: The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.

Adult↗
PubMed2005

Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials.

BACKGROUND: The T-20 Versus Optimized Background Regimen Only (TORO) 1 and TORO 2 clinical trials are open-label, controlled, parallel-group, phase 3 studies comparing enfuvirtide plus an optimized background (OB) of antiretrovirals (n = 661) with OB alone (n = 334) in treatment-experienced HIV-1-infected patients. METHODS: The primary objective at week 48 was to investigate durability of efficacy, as measured by the percentage of patients maintaining their week 24 response or improving. Efficacy analyses used the intent-to-treat population. RESULTS: A total of 73.7% of patients randomized to the enfuvirtide group remained on treatment through week 48 versus 21.3% originally randomized to the control group. At week 48, a higher proportion of week 24 responders maintained their response or were new responders in the enfuvirtide group than in the control group in each responder category: HIV-1 RNA level > or =1.0 log(10) change from baseline, <400 copies/mL and <50 copies/mL (37.4%, 30.4%, and 18.3% in the enfuvirtide group vs. 17.1%, 12.0%, and 7.8% in the control group, respectively; P < 0.0001 for all comparisons). CD4 cell count increases from baseline were twice as great in the enfuvirtide group as in the control group. CONCLUSION: These data demonstrate durable efficacy of enfuvirtide plus OB over 48 weeks.

Adolescent↗
PubMed2005

Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?

OBJECTIVES: Tubulopathy with hypophosphatemia have been observed in HIV-positive patients receiving a tenofovir-containing regimen. However, the real incidence and prevalence of hypophosphatemia and their relation to tubular reabsorption disorders in tenofovir-treated patients remain uncertain. The aim of our study was to explore the effect of tenofovir on phosphatemia and on tubular phosphate reabsorption. METHODS: In a first transversal study, 145 HIV-positive adults (44+/-9 years) receiving tenofovir 300 mg daily with a mean exposure of 11+/-9 months were included. In a second prospective study, 29 HIV-positive antiretroviral experienced adults (44+/-10 years) were evaluated before introduction of tenofovir 300 mg daily (M0) and at 3 months (M3) and 6 months (M6), thereafter. Phosphate, creatinine, glucose and protein levels were determined in plasma and urine. The ratio of maximal reabsorption capacity (TmPO4)/glomerular filtration rate (GFR) was determined by using the normogramm of Walton and Bijvoet. RESULTS: In the transversal study, 26% of patients had hypophosphatemia (<0.84 mmol/l) while 47% of patients had a decreased TmPO4/GFR (<0.8 mmol/l). In the prospective study, baseline prevalence of hypophosphatemia (<0.84 mmol/l) and decreased TmPO4/GFR (<0.8mmol/l) was 31 and 41%, respectively. Three and 6 months after starting tenofovir, there is no significant change in mean phosphate levels (M0:0.91 mmol/l, M3:0.97 mmol/l, M6:0.98 mmol/l) and mean TmPO4/GFR (M0:0.80 mmol/l, M3:0.88 mmol/l, M6:0.84 mmol/l). Moreover, prevalence of hypophosphatemia (M3:28%, M6:28%) and decreased TmPO4/GFR (M3:41%, M6:45%) remained stable. CONCLUSION: Hypophosphatemia linked to a decreased proximal tubular reabsorption was frequently observed in HIV-positive adults independently of the use of tenofovir. In this preliminary study, no worsening effect on phosphatemia and tubular phosphate reabsorption was observed 6 months after introduction of tenofovir in treatment experienced patients.

Adenine↗
PubMed2005

CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains.

The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.548, P<0.001). Yet, in vitro infection with either R5 or X4 strains and in vivo increases in viral load following interruption of antiretroviral treatment did not induce CXCR4 overexpression. The plasma levels of IL-7 and RANTES, 2 cytokines able to induce CXCR4 expression, did not correlate with CXCR4 density. Finally, higher CXCR4 densities were observed in patients harboring X4 strains (3300, 95% CI 2431-4169 CXCR4 molecules per cell) than in patients harboring only R5 strains (2406, 95% CI 2135-2677, P=0.027). These data suggest that CXCR4 overexpression during the course of the disease in some patients could favor the emergence of X4 strains.

Adolescent↗
PubMed2005

[New antiretroviral treatment modalities].

New treatment modalities for HIV infection in 2005 are based on the availability of new antiretrovirals and new strategies for their use. For reverse transcriptase inhibitors, abacavir/lamivudine and tenofovir/emtricitabine combinations minimize risks of mitochondrial toxicity and are now available as a single daily tablet. New protease inhibitors (PI) are boosted by ritonavir. Some that are already available (atazanavir, fosamprenavir) have good tolerance, resistance and dosing profiles. PIs in advanced stages of development (tipranavir and TMC114) specifically target strains with resistant mutations. Entry inhibitors affecting the CCR5 co-receptor are a new promising drug class. Enfuvirtide, a fusion inhibitor administered in subcutaneous injections, significantly improves the antiretroviral and immunologic response to antiretroviral regimens in patients with previous treatment failures. For successfully treated patients, simplification and treatment interruptions are sometimes possible. For non-responders, thorough virological-pharmacological assessment is necessary, together with access to new molecules and new drug classes.

Anti-Retroviral Agents↗
PubMed2005

T-Cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution. For this purpose, we compared CCR5 density, measured by quantitative flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase levels, and liver histology (inflammatory activity, fibrosis, and rate of fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV-coinfected individuals, did not correlate with any of the biologic parameters of HCV infection analyzed and was not linked to the capacity to clear the virus. In conclusion, we failed to demonstrate any impact of interindividual variability in T-cell surface CCR5 density on HCV infection, which would have argued against the use of CCR5 antagonists in HIV/HCV-coinfected subjects.

Adult↗
PubMed2005

Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance.

BACKGROUND: In HIV-infected patients on first-line antiretroviral therapy, the significance of intermittent viremia and their relationship with drug resistance remain unclear. OBJECTIVE: To study the virological characteristics of intermittent viremia (IV) and the association between IV and later virological failure (VF) in patients on a first-line, PI-containing therapy. STUDY DESIGN: Antiretroviral-naive patients were enrolled in the APROVIR substudy of the prospective, multicenter APROCO cohort at the time they initiated a PI-containing therapy and were followed-up at month 1 and every 2 months. IV was defined as plasma HIV-1 RNA > 500 copies/ml on a single specimen. VF were defined as: (1) viral rebound on two consecutive plasma specimens with HIV-1 RNA > 500 copies/ml after an initial response below 500 copies/ml, or (2) persistence of plasma HIV-1 RNA> or =500 copies/ml during the first year of follow-up. Genotypic resistance analysis was performed at baseline and at the time of IV. PI plasma concentrations were determined at the time of IV. RESULTS: IV was found in 20/219 patients in a 2 years follow-up. The occurrence of IV in the first year of therapy was associated with a higher risk of virological failure during the second year (p = 0.03). Genotypic resistance at the time of IV was found in only 4/16 patients and was not predictive of a subsequent virological failure. PI plasma levels suggested lack of adherence in 50% of patients with IV. CONCLUSION: The occurrence of IV > 500 copies/ml among patients on first-line, PI-containing ART is suggestive of a lack of adherence rather than the selection of resistant variants and should lead to an intensification of adherence monitoring in order to reduce the risk of subsequent VF.

Anti-HIV Agents↗
PubMed2004

[Human metapneumovirus pneumonia in an adult patient hospitalized for suspected severe acute respiratory syndrome (SARS)].

INTRODUCTION: Human metapneumovirus (hMPV) is a newly identified virus responsible for occasionally severe respiratory infections, mainly observed in children. OBSERVATION: A 59-year old man was hospitalised for respiratory problems and fever 3 days after his return from China during the epidemic of severe acute respiratory syndrome (SARS). Other than fever (>38 degrees C), the patient exhibited a dry cough, myalgias, arthralgias and mild lymphopenia and the chest radiography showed an opacity on the right lower lung. Conventional virological investigations remained negative. Detection of the novel SARS-associated coronavirus was negative but hMPV detection was positive. DISCUSSION: The present observation indicates that hMPV may cause respiratory symptoms mimicking initial manifestations of SARS in adults visiting epidemic countries. CONCLUSION: hMPV testing has clinical utility in adult patients with acute respiratory tract infection.

DNA, Viral↗
PubMed2004

Characterization of genotypic determinants in HR-1 and HR-2 gp41 domains in individuals with persistent HIV viraemia under T-20.

We analysed the genetic changes in gp41 in a population of 30 heavily pretreated HIV-1-infected patients failing on a T-20-containing salvage therapy. This study confirms the key role of the number of drugs presumed to be still effective associated with T-20 in the magnitude of the virological response. Our results suggest that only HR-1 sequencing is necessary to characterize resistance to T-20, and that HR-2 domain sequencing is probably not required.

Drug Resistance, Viral↗
PubMed2004

Comparison of drug resistance mutations and their interpretation in patients infected with non-B HIV-1 variants and matched patients infected with HIV-1 subtype B.

OBJECTIVE: To compare the prevalence of mutations associated with resistance to antiretroviral drugs and their interpretation in patients infected with non-B HIV-1 variants versus HIV-1subtype B-infected patients with similar treatment regimens. METHODS: The reverse transcriptase (RT) and protease genes of HIV-1 were sequenced, and subtypes were determined by phylogenetic analysis. Each sequence belonging to a non-B variant was matched with a sequence belonging to subtype B. Patterns of resistance mutations were interpreted in terms of drug resistance using the HIV db algorithm. RESULTS: RT mutations M41L, L210W, and, to a lesser extent, T215Y were less prevalent in patients infected with non-B variants. This lower prevalence was associated with subtypes A (A1/A2), C, F (F1/F2), and CRF06_cpx. A lower prevalence of high-level resistance to zidovudine was also observed in patients infected with these HIV-1 variants. In the protease gene, differences between patients infected with B or non-B strains were mainly observed for mutations playing a minor role in drug resistance and known to occur mainly as a natural polymorphism in non-B strains: K20R/M/I, M36I, L63P, A71V/T, and V77I. Interpretation of genotypes using the HIV db algorithm indicated that resistance to saquinavir, ritonavir, indinavir, and amprenavir was more frequently a high-level resistance for subtype B and an intermediate-level resistance for non-B variants, but this difference was only significant for amprenavir. CONCLUSION: Our results suggest that the genetic diversity of HIV-1 does not play a major role in the development of resistance to antiretroviral drugs.

Adult↗
PubMed2004

Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases.

We describe 7 cases of renal tubular injury in HIV-infected patients receiving an antiretroviral regimen containing tenofovir. Our patients (5 women and 2 men) developed renal tubular dysfunction, with hypophosphatemia, normoglycemic glycosuria, proteinuria, and decrease of creatinine clearance. The first biologic signs of renal toxicity were observed after duration of tenofovir treatment from 5 weeks to 16 months, and they resolved less than 4 months after discontinuation of tenofovir. Six patients had a low body weight (<60 kg). Five patients received low doses of ritonavir, and 1 received didanosine. In 5 patients, the signs resolved with the discontinuation of only the tenofovir. A renal biopsy performed in 1 patient was consistent with tubulointerstitial injury. Proximal tubulopathy appears to be a rare adverse effect of long-term tenofovir therapy. In patients with low weight or mild preexisting renal impairment, regular monitoring of tubulopathy markers could lead to early detection of this dysfunction.

Adenine↗